Clinically impactful research regarding HIV disease ultimately requires direct investigation of at-risk or HIV-infected human populations. Such human subjects-based research broadly includes, for example, ?bench to bedside? translational research, observational database-derived research, prospective cohort investigation, experimental work, and implementation science. Each of these research disciplines is sophisticated, requiring substantial infrastructure to pursue at the highest level. Some of the disciplines, such as translational research, require considerable coordination across several methodologic and substantive domains. To support clinically impactful research, particularly that which is translational, the overall objective of the UCSF-Gladstone CFAR Clinical and Population Sciences Core is to integrate the human subjects research methodologic disciplines of epidemiology and biostatistics with the basic and clinical substantive science of HIV infection to facilitate human subjects- based HIV-related research. Accordingly, the specific aims are to: Aim 1: Provide expertise in the clinical and population sciences related to HIV/AIDS research via consultation regarding conception of research questions, study design, sources of data, data management, biostatistical analysis, and interpretation of data; Aim 2: Manage unique prospective observational cohorts of HIV-infected adults in both San Francisco (SCOPE and Options) and Africa (UARTO and ISS Clinic Cohorts) that provide researchers with a diverse array of data and biological specimens from subjects who are well-characterized in terms of epidemiologic, clinical, laboratory and behavioral parameters; Aim 3: Offer a platform for the efficient conduct of newly proposed prospective human subjects studies; Aim 4: Mentor early stage investigators in the conduct of research involving human subjects. The rationale for a core mechanism to offer these services is to provide multiple researchers with a cost-efficient centralized resource that is not otherwise available through traditional funding sources. Evidence of the utility of the Core's approach in the current funding cycle includes distribution of over 24,000 biological specimen samples, support of 243 projects and 296 core users (including 124 early stage investigators), and facilitation of 184 publications in the past 4 years. In this proposed renewal, the central functions of the Core will be unchanged, with support of both domestic and international research, but several new additions and emphases are planned based on the institutional strengths at UCSF-Gladstone, the agendas of major NIH-sponsored HIV/AIDS programs, and the research initiatives being launched by local CFAR investigators.